This project aims to provide a translational model of adaptive and maladaptive responses to major stressors associated with trauma with the potential to not only provide novel insight into the etiology of PTSD but in addition to guide nove treatment developments for patients with PTSD. Our proposal aims to provide an integrative view on the functions of two major stress-response systems, the kappa opioid receptor system and glucocorticoids, which lays the foundation for future studies of these systems testing specific interventions for these patients. This proposal is a 3-year study involving thirty drug-naive participants in three study groups [PTSD, n=10; trauma-exposed healthy control subjects (TC), n=10; non trauma-exposed healthy control subjects (HC), n=10; age range 18-50 years, equal numbers of men and women in each cohort] who are to be recruited through public advertisement and invited to participate in a medical and psychiatric evaluation, neuroendocrine assessments, one MRI study and one PET study of kappa opioidreceptors using [11C]LY2795050 and PET. PUBLIC HEALTH RELEVANCE: This proposal aims to determine the potential role of kappa opioid receptors (k-OR) in the pathophysiology of PTSD. We propose to recruit patients with PTSD, as well as healthy control subjects with and without trauma exposure and will study k-ORs in vivo using the novel selective k-OR radioligand [11C]LY2795050 and positron emission tomography (PET). This study will for the first time determine the role of this opoid receptor subtype in PTSD and may lay the foundation for novel treatment developments for this patient population.